Incidental Mutation 'A5278:Rhou'
ID 64
Institutional Source Beutler Lab
Gene Symbol Rhou
Ensembl Gene ENSMUSG00000039960
Gene Name ras homolog family member U
Synonyms mG28K, WRCH-1, CDC42L1, WRCH1, 2310026M05Rik, Arhu
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # A5278 of strain 453
Quality Score
Status Validated
Chromosome 8
Chromosomal Location 124380668-124390623 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to T at 124387730 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Cysteine to Phenylalanine at position 154 (C154F)
Ref Sequence ENSEMBL: ENSMUSP00000038915 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000045487] [ENSMUST00000127664]
AlphaFold Q9EQT3
Predicted Effect probably damaging
Transcript: ENSMUST00000045487
AA Change: C154F

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000038915
Gene: ENSMUSG00000039960
AA Change: C154F

DomainStartEndE-ValueType
low complexity region 7 53 N/A INTRINSIC
RHO 55 228 5.59e-100 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000127664
SMART Domains Protein: ENSMUSP00000118564
Gene: ENSMUSG00000092329

DomainStartEndE-ValueType
Pfam:Glycos_transf_2 104 287 7.4e-31 PFAM
Pfam:Glyco_transf_7C 261 331 4.9e-8 PFAM
RICIN 406 531 9.28e-27 SMART
Coding Region Coverage
  • 1x: 88.2%
  • 3x: 73.8%
Validation Efficiency 87% (116/134)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the Rho family of GTPases. This protein can activate PAK1 and JNK1, and can induce filopodium formation and stress fiber dissolution. It may also mediate the effects of WNT1 signaling in the regulation of cell morphology, cytoskeletal organization, and cell proliferation. A non-coding transcript variant of this gene results from naturally occurring read-through transcription between this locus and the neighboring DUSP5P (dual specificity phosphatase 5 pseudogene) locus.[provided by RefSeq, Mar 2011]
Allele List at MGI

All alleles(2) : Targeted, other(2)

Other mutations in this stock
Total: 7 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Kat14 C A 2: 144,235,227 (GRCm39) S18* probably null Het
Kif17 T C 4: 138,015,261 (GRCm39) V278A probably benign Homo
Myo3a A G 2: 22,328,464 (GRCm39) T353A probably benign Het
Pbk T A 14: 66,051,388 (GRCm39) I142N probably damaging Het
Rab32 A G 10: 10,433,717 (GRCm39) I39T possibly damaging Het
Slc4a1 A G 11: 102,244,641 (GRCm39) probably benign Het
Tdrd7 C T 4: 46,007,622 (GRCm39) T558M probably benign Homo
Other mutations in Rhou
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01726:Rhou APN 8 124,380,880 (GRCm39) missense possibly damaging 0.60
R0926:Rhou UTSW 8 124,387,715 (GRCm39) missense probably damaging 1.00
R1467:Rhou UTSW 8 124,388,029 (GRCm39) missense possibly damaging 0.94
R1467:Rhou UTSW 8 124,388,029 (GRCm39) missense possibly damaging 0.94
R1873:Rhou UTSW 8 124,387,990 (GRCm39) missense probably damaging 1.00
R2276:Rhou UTSW 8 124,382,258 (GRCm39) missense probably damaging 1.00
R2937:Rhou UTSW 8 124,387,880 (GRCm39) missense possibly damaging 0.65
R5107:Rhou UTSW 8 124,387,912 (GRCm39) nonsense probably null
R5176:Rhou UTSW 8 124,380,848 (GRCm39) missense possibly damaging 0.90
R6172:Rhou UTSW 8 124,387,903 (GRCm39) missense probably benign 0.07
R7053:Rhou UTSW 8 124,380,934 (GRCm39) intron probably benign
R9185:Rhou UTSW 8 124,387,793 (GRCm39) missense probably damaging 1.00
R9741:Rhou UTSW 8 124,380,914 (GRCm39) missense possibly damaging 0.46
Nature of Mutation
DNA sequencing using the SOLiD technique identified a G to T transversion at position 478 of the Rhou transcript in exon 3 of 3 total exons. The mutated nucleotide causes a cysteine to phenylalanine substitution at amino acid 154 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Rhou gene encodes a 261 amino acid Rho-related GTP-binding protein. RHOU acts upstream of PAK1 to regulate the actin cytoskeleton, adhesion turnover and increase cell migration. It also stimulates quiescent cells to reenter the cell cycle. The RHOU protein has no detectable GTPase activity, but its high intrinsic guanine nucleotide exchange activity suggests it is constitutively GTP-bound. GTP binding occurs at amino acids 59-66, 106-110, and 164-167 (Uniprot Q9EQT3).
 
The C154F change is predicted to be probably damaging by the PolyPhen program.
Posted On 2009-12-03